VEGF regulates FGF-2 and TGF-beta1 expression in injury endothelial cells and mediates smooth muscle cells proliferation and migration.
BACKGROUND
Vascular endothelial growth factor (VEGF) is implicated in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA) as well as atherosclerosis. The purpose of our study was: 1) to evaluate the expression of endothelial cell (EC) fibroblast growth factor 2 (FGF-2) and transforming growth factor beta1 (TGF-beta1) mRNA expression following vascular injury and VEGF modulation and 2) to assess whether VEGF indirectly stimulates smooth muscle cell (SMC) migration and proliferation via growth factors released by injured EC.


METHODS
Bovine aortic endothelial cells (BAEC) were cultured to near confluency and were serum starved. Linear wounds were made in medium with and without VEGF. FGF-2 and TGF-beta1 mRNA expression were evaluated. Bovine aortic organ culture experiments were also carried out and growth factor expression was assessed. SMC proliferation and migration was assessed in response to EC injury medium with/without VEGF.


RESULTS
EC injury in the presence of VEGF increased FGF-2 mRNA. EC injury also induced TGF-beta1 mRNA expression; however VEGF inhibited TGF-beta1 mRNA expression in both injured and noninjured ECs. VEGF increased FGF-2 mRNA stability and did not alter TGF-beta1 mRNA stability. SMC proliferation and migration was found to be induced by injured EC media and injury EC medium with VEGF, respectively


CONCLUSIONS
The results demonstrate that 1) VEGF indirectly stimulates SMC proliferation and migration through stimulation of the expression of FGF-2 and 2) VEGF inhibits the expression of TGF-beta1 released by EC. Theses data further suggest an integral role for FGF-2 and TGF-beta1 in wound repair.
Li
Dongmei
D
Harbin Medical University, 194 Xuefu Lu, Harbin 150081, China.
Zhang
Cuili
C
Song
F
F
Lubenec
I
I
Tian
Ye
Y
Song
Q H
QH
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D001483:Base Sequence; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects*; D009924:Organ Culture Techniques; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D017931:DNA Primers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2